Is ABCB9 p.Val197Met (c.589G>A) pathogenic?

ABCB9 p.Val197Met (c.589G>A) is classified Uncertain significance in ABCB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.0986); Very rare (popmax 0.00681%, eas).

How common is ABCB9 p.Val197Met (c.589G>A) in the general population?

ABCB9 p.Val197Met (c.589G>A) is very rare (popmax 0.00681%, eas) (gnomAD).

What do computational predictors say about ABCB9 p.Val197Met (c.589G>A)?

AlphaMissense predicts likely benign (score 0.0986) — an in-silico prediction, not a clinical call.

ABCB9 p.Val197Met

c.589G>A · VCV4636106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00681%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0986	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4.8
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.00058 · regional, not allelic
Overall
CADD	16.93	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00681% East Asian · 3/44,066 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00128% 20/1,560,944 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00681%	14,689
African / African-American	0.00408%	24,516
Admixed American	0.00185%	54,172
Remaining individualsnot grpmax-eligible	0.00166%	60,092
European (non-Finnish)	0.00104%	95,772

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCB9
Protein: p.Val197Met
Coding: c.589G>A
MANE Select: NM_019625
Type: single nucleotide variant
Location: chr12:122959647 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.76
Residue 197: the abc transmembrane type-1 domain

Full ABCB9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ABCB9 p.Ala368Val Uncertain significance ★ ⚠ same type
ABCB9 p.Ala447Thr Uncertain significance ★ ⚠ same type
ABCB9 p.Ala641Ser Uncertain significance ★ ⚠ same type
ABCB9 p.Ala641Thr Uncertain significance ★ ⚠ same type
ABCB9 p.Ala64Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcb9-p-val197met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown